Advancing Potential Therapies for Age-Related Macular Degeneration
New research uncovers the role of heparan sulfate in trapping lipoproteins that lead to early stages of age-related macular degeneration. Discover promising therapeutic strategies to prevent vision loss.
Age-related macular degeneration (AMD) remains a leading cause of vision loss among the elderly, characterized initially by the formation of drusen—deposits composed of lipids and proteins that accumulate between the retina's layers, specifically the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). These deposits are not only indicative of the disease but actively contribute to retinal deterioration, impairing vision.
Recent research highlights the role of lipoproteins, such as high-density lipoprotein (HDL), in drusen formation. It has been unclear why these lipoproteins become trapped within BrM in early AMD cases. A groundbreaking study published in the Proceedings of the National Academy of Sciences, led by Dr. Christopher B. Toomey from UC San Diego, sheds light on this process. The research suggests that heparan sulfate (HS) in BrM plays a critical role by binding and trapping lipoproteins, thus initiating drusen development. If this interaction can be mitigated, it may open avenues for preventing or even reversing early AMD stages.
Key findings from the study include elevated levels of HS in the macular region of BrM in AMD patients compared to healthy controls. Lipoprotein-like particles were observed to aggregate in HS-rich areas, and using heparin—an HS analog—they effectively washed out these particles from AMD tissue, confirming HS's role as a sticky trap. When HS was removed or blocked with specialized molecules, lipoprotein binding was significantly reduced, indicating potential therapeutic strategies.
The research also highlights the potential of non-blood-thinning heparin-like compounds to dissolve harmful lipoproteins without increasing bleeding risks, offering promising new treatment pathways. Such therapies could target early drusen formation, possibly preventing progression to severe vision loss.
This innovative work opens the door for developing targeted treatments that interfere with lipoprotein trapping in BrM, addressing the root cause of drusen buildup and AMD progression.
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